Head-to-head comparison of the diagnostic performance between 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer: a systematic review and meta-analysis.

This study aimed to compare the detection rates of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer. A systematic search of major medical databases was conducted to identify studies up to September 2023. The primary outcome assessed was the detection rate of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in the primary tumor. Pooled risk ratios with a 95% CI were calculated using random-effect models to adjust for heterogeneity. Eight studies were included in the meta-analysis. 68Ga-FAPI-04 PET/CT has higher uptakes in lymph nodes, bone, and peritoneal metastasis compared with 18F-FDG PET/CT. The detection rate of 68Ga-FAPI-04 PET/CT based on lesion was better for lymph node metastasis (RR = 0.63, 95% CI 0.47-0.84, P = 0.002) and peritoneal metastasis (RR = 0.52, 95% CI 0.32-0.85, P = 0.009), both imaging modalities had essentially the same diagnostic efficacy in primary tumor (RR = 0.99, 95% CI 0.96-1.02, P = 0.49). 68Ga-FAPI-04 as a highly promising PET/CT tracer was superior to 18F-FDG PET/CT in colorectal cancer, especially in detecting lymph node metastases and peritoneal metastases.

T2WI-based texture analysis predicts preoperative lymph node metastasis of rectal cancer.

BACKGROUND: To prospectively develop and validate the T2WI texture analysis model based on a node-by-node comparison for improving the diagnostic accuracy of lymph node metastasis (LNM) in rectal cancer. METHODS: A total of 381 histopathologically confirmed lymph nodes (LNs) were collected. LNs texture features were extracted from MRI-T2WI. Spearman's rank correlation coefficient and the least absolute shrinkage and selection operator were used for feature selection to construct the LN rad-score. Then the clinical risk factors and LN texture features were combined to establish combined predictive model. Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Decision curve analysis (DCA) and nomogram were used to evaluate the clinical application of the model. RESULTS: A total of 107 texture features were extracted from LN-MRI images. After selection and dimensionality reduction, the radiomics prediction model consisting of 8 texture features showed well-predictive performance in the training and validation cohorts (AUC, 0.676; 95% CI 0.582-0.771) (AUC, 0.774; 95% CI 0.648-0.899). A clinical-radiomics prediction model with the best performance was created by combining clinical and radiomics features, 0.818 (95% CI 0.742-0.893) for the training and 0.922 (95% CI 0.863-0.980) for the validation cohort. The LN Rad-score in clinical-radiomics nomogram obtained the highest classification contribution and was well calibrated. DCA demonstrated the superiority of the clinical-radiomics model. CONCLUSION: The lymph node T2WI-based texture features can help to improve the preoperative prediction of LNM.

Can Organoid Model Reveal a Key Role of Extracellular Vesicles in Tumors? A Comprehensive Review of the Literature.

Extracellular vesicles (EVs) are small membrane-bound vesicles that are released by cells into the extracellular environment. The role of EVs in tumors has been extensively studied, and they have been shown to play a crucial role in tumor growth, progression, and metastasis. Past research has mainly used 2D-cultured cell line models to investigate the role of EVs in tumors, which poorly simulate the tumor microenvironment. Organoid technology has gradually matured in recent years. Organoids are similar in composition and behavior to physiological cells and have the potential to recapitulate the architecture and function of the original tissue. It has been widely used in organogenesis, drug screening, gene editing, precision medicine and other fields. The integration of EVs and organoids has the potential to revolutionize the field of cancer research and represents a promising avenue for advancing our understanding of cancer biology and the development of novel therapeutic strategies. Here, we aimed to present a comprehensive overview of studies using organoids to study EVs in tumors.

Global Status of Research on Lateral Lymph Nodes in Rectal Cancer from 1994 to 2022: A Bibliometric Analysis.

Tremendous progress has been made in the field of lateral lymph nodes (LLNs) in rectal cancer, but no bibliometric analysis in this field has been carried out and published. To reveal the current status and trends in LLNs in rectal cancer, this bibliometric analysis was performed. Cooperation network, co-citation and keyword co-occurrence analyses were conducted. Annual publication, cooperation relationships among authors, institutions and countries, co-cited journal, co-cited author, co-cited reference and keywords were the main outcomes. A total of 345 studies were included in this bibliometric analysis. The number of articles published in this field has been increasing year by year. The authors, institutions and countries worked closely together in this field. Japan has the largest number of published articles, accounting for 51.59% of the total publications. International Journal of Colorectal Disease (30 papers, 8.70%) published the most papers in this field. The JCOG0212 trial was the most cited article. Preoperative chemoradiotherapy, multicenter, lateral lymph node dissection (LLND) and metastasis are recent hot keywords, and LLND had the highest burst strength. In conclusion, this bibliometric analysis found that Japanese institutions and authors dominated the field of LLNs in rectal cancer. The JCOG0212 trial was the most influential article, which had a significant impact on the development of guidelines. LLND is a hotspot in this field with the highest burst strength. Further prospective studies are needed in this field.

The effect of BMI on long-term outcome in patients with rectal cancer and establishment of a nomogram prediction model.

BACKGROUND: The effects of body mass index (BMI) in patients with rectal cancer have been poorly studied and are still controversial. In this study, we aimed to assess the effect of BMI on the long-term outcome in patients with rectal cancer after radical surgery. MATERIALS AND METHODS: Between April 2012 and December 2020, patients who received total mesorectal excision (TME) surgery were enrolled in the study. Patients were divided into four groups according to BMI level. Kaplan-Meier survival curves with log-rank tests were used to analyze overall survival (OS), Disease-free survival (DFS), local recurrence-free survival and distant metastasis-free survival. Univariate and multivariate analyses were performed to identify the risk factors associated with the long-term outcome. Nomograms were developed to predict the OS and DFS based on independent prognostic factors. RESULTS: A total of 688 patients were included in this study. The median follow-up time was 69 months. The 5-year OS rates of the control, underweight, overweight and obese groups were 79.2%, 62.2%, 88.7% and 86.3%, respectively. The 5-year DFS rates were 74.8%, 58.2%, 80.5% and 81.4%, respectively. Overweight (HR 0.534; 95% CI 0.332-0.860, p = 0.010) was an independent protective factor for OS and DFS (HR 0.675; 95% CI 0.461-0.989, p = 0.044). Underweight was an independent risk factor for DFS (HR = 1.623; 95% CI 1.034-2.548; p = 0.035), and had a trend to be an independent risk factor for OS (HR 1.594; 95% 0.954-2.663; p = 0.075). Nomograms were established to predict the 2-year OS, 5-year OS, 2-year DFS and 5-year DFS with an area under curve (AUC) of 0.767, 0.712, 0.746 and 0.734, respectively. CONCLUSIONS: For rectal cancer patients after radical surgery, overweight was an independent protective factor for OS and DFS. Underweight was an independent risk factor for DFS and had a trend to be an independent risk factor for OS. Nomograms incorporating BMI and other prognostic factors could be helpful to predict long-term outcome.

Adenosine causes short-lasting vasodilation and headache but not migraine attacks in migraine patients: a randomized clinical trial.

ABSTRACT: Migraine is a common disabling disease with a complex pathophysiology. Headache is a frequent side effect after intravenous adenosine administration, although adenosine receptor antagonist, caffeine, relieves migraine headache. These observations suggest a possible involvement of adenosine signaling in headache and migraine pathophysiology. In a randomized, double-blinded, placebo-controlled, crossover study, 18 participants diagnosed with migraine without aura received 120 µg/kg per minute adenosine or placebo over 20 minutes. Headache intensity, migraine-associated symptoms, vital signs, the diameter of the superficial temporal artery (STA), blood flow velocity in the middle cerebral artery (V MCA ), and facial skin blood flow were measured at baseline and every 10 minutes until 2 hours after infusion start. The primary end point was the difference in the incidence of migraine attacks after adenosine infusion compared with placebo. Eighteen participants completed the study. We found no difference in the incidence of migraine after adenosine infusion (7 of 18, 39%) compared with placebo (3 of 18, 17%) ( P = 0.29). Fourteen participants reported headache after adenosine infusion (14 of 18, 78%) compared with placebo (6 of 18, 33%) ( P < 0.01). Adenosine increased heart rate ( P < 0.001), facial skin blood flow ( P < 0.05), and STA diameter (AUC T0-20min , P = 0.01) and decreased V MCA (AUC T0-20min , P < 0.001) compared with placebo. Adenosine induced headache accompanied by a short-lasting (<30 minutes) dilation of intracerebral and extracerebral arteries. The nonsignificant migraine induction might be because of the presence of several adenosine receptors with counteracting signaling, highlighting the need of more selective modulators to dissect the implication of adenosine in migraine.

The diagnostic value of exosomal circular RNAs in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the potential to be novel biomarkers for cancer diagnosis. This study aims to summarize the role of exosomal circRNAs in cancer diagnosis by a meta-analysis. METHODS: A comprehensive literature search was conducted up to July 2021 in PubMed, Web of Science, EMBASE, and Cochrane Database. To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance. RESULTS: Ten eligible studies with 514 controls and 557 patients were included in this diagnostic meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.75 (95% CI: 0.65-0.83), 0.84 (95% CI, 0.78-0.89), 5.87 (95% CI, 3.67-9.38), 0.28 (95% CI, 0.19-0.40), and 21.15 (95% CI, 10.25-43.68), respectively. The AUC was 0.89 (95% CI, 0.86-0.91). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability of 20%, the post probability positive, the post probability negative were 59% and 6%, respectively. CONCLUSION: Our results suggested that exosomal circRNAs might serve as powerful biomarkers in detecting cancers with high sensitivity and specificity. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

Technique to match mesorectal lymph nodes imaging findings to histopathology: node-by-node comparison.

BACKGROUND: Lymph node status is critical for staging rectal cancer and determining neoadjuvant therapy regimens. Establishing a matching between imaging and histopathological lymph nodes is fundamental for predicting lymph node status. This study reports a technique to achieve node-by-node pairing of mesorectal lymph nodes between imaging findings and histopathology. METHODS: Fifty-two patients with histopathologically verified rectal cancer underwent magnetic resonance imaging before surgery. The status of each lymph node in the surgical specimens was analyzed histopathologically and matched with preoperative imaging after the operation. RESULTS: A total of 346 mesorectal lymph nodes were located on imaging evaluation, of which 313 were confirmed histopathologically, and 33 were unmatched. The total success rate of the technique was 90.5%. Node-by-node analysis revealed 280 benign and 33 malignant nodal structures. CONCLUSION: The technique to match mesorectal lymph node imaging findings to histopathology was feasible and effective. It simplified the technical method and had a reasonable success matching rate, which could provide a standardized approach for obtaining a prospective correlation between imaging and histological findings, supporting all subsequent related studies at the level of mesorectal lymph nodes.

Comprehensive Analysis of Potential Prognostic Values of ANGPTLs in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. CRC recurrence and metastasis cause poor prognosis. ANGPTLs (angiopoietin-like proteins) are a family of proteins that are widely involved in metabolic disease and tumorigenesis. The roles of ANGPTLs in CRC are still controversial and deserve further research. In this study, several databases were employed to explore the expression profiles, prognostic values, genetic alterations, potential biological function, and immune infiltration correlation of ANGPTLs in CRC. The expression of ANGPTL4 was significantly positively correlated with the stage of CRC. Therefore, cell and molecular experiments were further performed to explore the roles of ANGPTL4. Our results showed that the transcriptions of ANGPTLs in colon cancer and rectal cancer tissues were lower than those in normal tissues, but the protein expression varied among different ANGPTLs. In addition, the high expression of ANGPTLs led to a relatively poor oncological outcome. Specifically, the expression of ANGPTL4 is significantly positively correlated with the stage of CRC. Further investigation revealed that ANGPTLs are mainly involved in signal transduction and the regulation of transcription, while KEGG pathway analyses demonstrated pathways in cancer. Additionally, we also observed that ANGPTL4 could promote the proliferation and migration of CRC cells, and four specific small molecule compounds had potential ANGPTL4-binding capabilities, suggesting the clinical application of these small molecule compounds on CRC treatment. Our findings imply the prognostic values and potential therapeutic targets of ANGPTLs in CRC.

Establishment and validation of nomograms for predicting mesorectal lymph node staging and restaging.

BACKGROUND: Preoperative determination of lymph node (LN) status is crucial in treatment planning for rectal cancer. This study prospectively evaluated the risk factors for lymph node metastasis (LNM) at staging and restaging based on a node-by-node pairing between MRI imaging findings and histopathology and constructed nomograms to evaluate its diagnostic value. METHODS: From July 2021 to July 2022, patients with histopathologically verified rectal cancer who underwent MRI before surgery were prospectively enrolled. Histological examination of each LN status in the surgical specimens and anatomical matching with preoperative imaging. Taking histopathological results as the gold standard, federating clinical features from patients and LN imaging features on MRI-T2WI. Risk factors for LN metastasis were identified by multivariate logistic regression analysis and used to create a nomogram. The performance of the nomograms was assessed with calibration plots and bootstrapped-concordance index and validated using validation cohorts. RESULTS: A total of 500 target LNs in 120 patients were successfully matched with node-by-node comparisons. A total of 353 LNs did not receive neoadjuvant therapy and 147 LNs received neoadjuvant chemoradiotherapy (neoCRT). Characterization of LNs not receiving neoadjuvant therapy and multivariate regression showed that the short diameter, preoperative CEA level, mrT-stage, border contour, and signal intensity were associated with a high risk of LN metastasis (P < 0.05). The nomogram predicted that the area under the curve was 0.855 (95% CI, 0.794-0.916) and 0.854 (95% CI, 0.727-0.980) in the training and validation cohorts, respectively. In the neoadjuvant therapy group, short diameter, ymrT-stage, internal signal, and MRI-EMVI were associated with LN positivity (P < 0.05), and the area under the curves using the nomogram was 0.912 (95% CI, 0.856-0.968) and 0.915 (95% CI, 0.817-1.000) in two cohorts. The calibration curves demonstrate good agreement between the predicted and actual probabilities for both the training and validation cohorts. CONCLUSION: Our nomograms combined with preoperative clinical and imaging biomarkers have the potential to improve the prediction of nodal involvement, which can be used as an essential reference for preoperative N staging and restaging of rectal cancer.

Single-nucleotide polymorphisms in genes related to oxidative stress and ion channels in chickens are associated with semen quality and hormonal responses to thermal stress.

Heat stress causes economic loss of livestock industry in tropical areas. Exploring genetic markers for selection of thermotolerance will benefit chicken production. Oxidative stress and fluid-salt balance are tightly associated with thermotolerance and productivity in domestic animals. The study aimed to identify single-nucleotide polymorphisms (SNPs) in genes related to oxidative stress and ion-channel regulation and their associations with semen quality and hormonal responses. In total, 28 SNPs within 11 candidate genes were identified to associate with hormonal changes and semen quality in both broiler- and layer-type Taiwan country chickens (TCCs) after exposure to acute heat stress at 38 °C for 4 h. Acute heat stress significantly affected plasma levels of triiodothyronine and corticosterone and reduced sperm motility, viability, and concentrations in both strains at Day 1 after exposure. In the B-strain TCCs, five SNPs within NDUFA8 and DAB2IP had significant effects on plasma adrenaline and corticosterone levels, and six SNPs within TRPC1, SLC9A9, and TRPC7 markedly affected plasma corticosterone and triiodothyronine levels. In the L2 strain, 15 SNPs within PSMA2, TPK1, MTF1, and CUL1 exerted effects on plasma corticosterone and triiodothyronine levels. Five SNPs within CUL3, TRPC1, and SLC9A9 in the B strain and two SNPs within MTF1 in the L2 strain were associated with sperm concentrations at Day 1 after exposure to heat stress. In conclusion, acute heat stress impaired semen quality and altered plasma corticosterone and triiodothyronine levels in TCCs. Some SNPs involved in oxidative stress and ion-channel regulation were identified to associate with the hormonal and semen alterations. These SNPs in conjunction with differential hormonal responses and semen quality serve as genetic markers for thermotolerance selection in sire lines of chickens.

The Key Role of Exosomes on the Pre-metastatic Niche Formation in Tumors.

Exosomes or other extracellular vesicles released from cells play an important role in cell-to-cell communication by transferring bio-information (DNA, coding/non-coding RNA, and proteins), which indicates parental cell status to recipient cells in the extracellular environment. Increasingly, evidence shows that tumor-derived exosomes mediate tumor pre-metastatic niche (PMN) remodeling to establish a supportive and receptive niche to promote tumor cell colonization and metastasis. Uptake of genetic information by target cells in the extracellular environment triggers epigenetic changes that contribute to PMN formation. Here, we provide a comprehensive overview of the current understanding of exosomes-mediated reprogramming of cells in PMN formation.

Co-pathogens in Periodontitis and Inflammatory Bowel Disease.

Localized inflammatory lesions in one area of the body may affect other distant organs through various modes of transmission thus initiating secondary inflammatory infections. Periodontal disease (PD) and inflammatory bowel disease (IBD) have been shown to coexist. Periodontitis is a multifactorial inflammatory disease, and dental plaque is considered to be the initial risk factor. Individuals with genetic susceptibility are more likely to develop periodontitis when exposed to external stimuli. IBD is affected by host genetics, immunoregulation, daily diet, and the gut microbiota, and its risk factors appear to be shared with those of PD. However, the key etiologies of both diseases remain unclear, thus hindering the exploration of possible links between IBD and PD. Recent studies and systematic reviews have focused on evidence-based statistics of the prevalence and clinical manifestations of both diseases, but discussions of the microbial etiological correlation between periodontitis and intestinal inflammation are scarce. Here, we summarize the potential common pathogenic microorganisms that may serve as bridges between the two diseases. Studies have shown that invasive microorganisms such as Porphyromonas gingivalis, Fusobacterium nucleatum, Klebsiella spp. and Campylobacter spp. play key roles in the comorbidity of PD and IBD.

Open versus laparoscopic lateral lymph node dissection for mid- and low- rectal cancer: a propensity score matching study.

BACKGROUND: This study aimed to evaluate the perioperative, pathological and oncological outcomes of open versus laparoscopic total mesorectal excision (TME) plus lateral lymph node dissection (LLND) for mid- and low- rectal cancer using propensity score matching. METHODS: Between September 2009 and December 2018, consecutive patients who underwent open or laparoscopic TME plus LLND were collected. Based on the propensity score matching analysis, laparoscopic TME plus LLND was compared with open TME plus LLND for the perioperative, pathological, and oncological outcomes. RESULTS: A total of 77 patients were collected. There were 13 patients who underwent open TME plus LLND (open group) and 64 patients who underwent laparoscopic TME plus LLND (laparoscopic group). After propensity score matching, 13 patients in the open group were matched to 39 patients in the laparoscopic group (1:3). The laparoscopic group had a significantly shorter length of incision (5 cm vs. 20 cm, p < 0.01), less intraoperative blood loss (80 mL vs. 100 mL, p = 0.02), and shorter time to postoperative liquid diet (72 h vs. 96 h, p = 0.05). There were no significant differences in both early and late postoperative complications. The 3-year overall survival was 85.9% in the laparoscopic group and 76.9% in the open group (p = 0.75), respectively. The 3-year disease-free survival was 70.6% in the laparoscopic group and 74.1% in the open group (p = 0.83), respectively. CONCLUSION: Laparoscopic LLND had comparable oncological outcomes to open LLND. Moreover, laparoscopic LLND had postoperative recovery advantages over open LLND.

Long-term outcome of indwelling colon observed seven years after radical resection for rectosigmoid cancer: A case report.

BACKGROUND: Indwelling colon is characterized by an excluded segment of the colon after surgical diversion of the fecal stream with colostomy so that contents are unable to pass through this part of the colon. We report a rare case of purulent colonic necrosis that occurred 7 years after surgical colonic exclusion. CASE SUMMARY: A 73-year-old male had undergone extended radical resection for rectosigmoid cancer. The invaded ileocecal area and sigmoid colon were removed during the procedure, and the ileum was anastomosed side-to-side with the rectum. The excluded ascending, transverse, and descending colon were sealed at both ends and left in the abdomen. After 7 years, the patient developed persistent abdominal pain and distension. Work-up indicated intestinal obstruction. The patient underwent ultrasound-guided catheter drainage of the descending colon and a large amount of viscous liquid was drained, but the symptoms persisted; therefore, surgery was planned. Intraoperatively, extensive adhesions were found in the abdominal cavity, and the small intestine and the indwelling colon were widely dilated. The dilated colon was 56 cm long, 5 cm wide (diameter), and contained about 1500 mL of viscous liquid. The indwelling colon was surgically removed and its histopathological examination revealed colonic congestion and necrosis with hyperplasia of granulation tissue. The bacterial culture of the secretions was negative. The patient recovered after the operation. CONCLUSION: Although colonic exclusion is routinely performed, this report aimed to increase awareness regarding the possible long-term complications of indwelling colon.

Magnetic Resonance Imaging Evaluation of the Accuracy of Various Lymph Node Staging Criteria in Rectal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Magnetic resonance imaging (MRI)-based lymph node staging remains a significant challenge in the treatment of rectal cancer. Pretreatment evaluation of lymph node metastasis guides the formulation of treatment plans. This systematic review aimed to evaluate the diagnostic performance of MRI in lymph node staging using various morphological criteria. METHODS: A systematic search of the EMBASE, Medline, and Cochrane databases was performed. Original articles published between 2000 and January 2021 that used MRI for lymph node staging in rectal cancer were eligible. The included studies were assessed using the QUADAS-2 tool. A bivariate random-effects model was used to conduct a meta-analysis of diagnostic test accuracy. RESULTS: Thirty-seven studies were eligible for this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of preoperative MRI for the lymph node stage were 0.73 (95% confidence interval [CI], 0.68-0.77), 0.74 (95% CI, 0.68-0.80), and 7.85 (95% CI, 5.78-10.66), respectively. Criteria for positive mesorectal lymph node metastasis included (A) a short-axis diameter of 5 mm, (B) morphological standard, including an irregular border and mixed-signal intensity within the lymph node, (C) a short-axis diameter of 5 mm with the morphological standard, (D) a short-axis diameter of 8 mm with the morphological standard, and (E) a short-axis diameter of 10 mm with the morphological standard. The pooled sensitivity/specificity for these criteria were 75%/64%, 81%/67%, 74%/79%, 72%/66%, and 62%/91%, respectively. There was no significant difference among the criteria in sensitivity/specificity. The area under the receiver operating characteristic (ROC) curve values of the fitted summary ROC indicated a diagnostic accuracy rate of 0.75-0.81. CONCLUSION: MRI scans have minimal accuracy as a reference index for pretreatment staging of various lymph node staging criteria in rectal cancer. Multiple types of evidence should be used in clinical decision-making.

Effects of acute heat stress on protein expression and histone modification in the adrenal gland of male layer-type country chickens.

The adrenal gland responds to heat stress by epinephrine and glucocorticoid release to alleviate the adverse effects. This study investigated the effect of acute heat stress on the protein profile and histone modification in the adrenal gland of layer-type country chickens. A total of 192 roosters were subject to acute heat stress and thereafter classified into a resistant or susceptible group according to body temperature change. The iTRAQ analysis identified 80 differentially expressed proteins, in which the resistant group had a higher level of somatostatin and hydroxy-δ-5-steroid dehydrogenase but a lower parathymosin expression in accordance with the change of serum glucocorticoid levels. Histone modification analysis identified 115 histone markers. The susceptible group had a higher level of tri-methylation of histone H3 lysine 27 (H3K27me3) and showed a positive crosstalk with K36me and K37me in the H3 tails. The differential changes of body temperature projected in physiological regulation at the hypothalamus-pituitary-adrenal axis suggest the genetic heterogeneity in basic metabolic rate and efficiency for heat dissipation to acclimate to thermal stress and maintain body temperature homeostasis. The alteration of adrenal H3K27me3 level was associated with the endocrine function of adrenal gland and may contribute to the thermotolerance of chickens.

Hypersensitivity to calcitonin gene-related peptide in chronic migraine.

OBJECTIVE: To investigate if calcitonin gene-related peptide infusion induces migraine-like attacks in chronic migraine patients. METHODS: Fifty-eight patients with chronic migraine, either with or without headache on the experimental day, were assessed for the incidence of migraine-like attacks after an intravenous infusion with calcitonin gene-related peptide 1.5 µg/min over 20 min. The primary endpoint was the incidence of migraine-like attacks after calcitonin gene-related peptide. Exploratory endpoints were the association between the incidence of migraine-like attacks and presence of headache on the experimental day, and headache frequency in the past month. Migraine-like attack data was compared to a historic cohort of 91 episodic migraine patients without headache on the experimental day. Total tenderness score, pressure-pain threshold and supra-threshold pressure pain at baseline were investigated in relation to incidence of migraine-like attacks and presence of headache on the experimental day. RESULTS: In total, 83% of the 58 chronic migraine patients developed migraine-like attacks after calcitonin gene-related peptide infusion. Migraine-like attacks were found in 92% of chronic migraine patients with headache on the experimental day compared to 65% of chronic migraine patients without headache on the experimental day (p = 0.035). No differences were observed in total tenderness score and pressure-pain threshold between chronic migraine patients with and without headache on the experimental day. The incidence of migraine-like attacks following calcitonin gene-related peptide in chronic migraine patients without headache (65%) was equal to the historic cohort of 91 episodic migraine patients without headache (67%) on the experimental day. CONCLUSIONS: Chronic migraine patients are hypersensitive to calcitonin gene-related peptide. The potency of calcitonin gene-related peptide as a migraine inductor is increased in chronic migraine patients with ongoing headache. We suggest that calcitonin gene-related peptide, besides being a migraine trigger also acts as a modulator of nociceptive transmission in the trigeminal system.

Genomic regions and pathways associated with thermotolerance in layer-type strain Taiwan indigenous chickens.

This study aimed to investigate genetic markers and candidate genes associated with thermotolerance in a layer-type strain Taiwan indigenous chickens exposed to acute heat stress. One hundred and ninety-two 30-week-old roosters were subjected to acute heat stress. Changes in body temperature (BT, ΔT) were calculated by measuring the difference between the initial BT and the highest BT during heat stress and the results were categorized into dead, susceptible, tolerant, and intermediate groups depending on their survival and ΔT values at the end of the experiment. A genome-wide association study on survival and ΔT values was conducted using the Cochran-Armitage trend test and Fisher's exact test. Association analyses identified 80 significant SNPs being annotated to 23 candidate genes, 440 SNPs to 71 candidate genes, 64 SNPs to 25 candidate genes, and 378 SNPs to 78 candidate genes in the dead versus survivor, tolerant versus susceptible, intermediate versus tolerant, and intermediate versus susceptible groups, respectively. The annotated genes were associated with apoptosis, cellular stress responses, DNA repair, and metabolic oxidative stress. In conclusion, the identified SNPs of candidate genes provide insights into the potential mechanisms underlying physiological responses to acute heat stress in chickens.

Genome-wide association study on the body temperature changes of a broiler-type strain Taiwan country chickens under acute heat stress.

Body temperature is the simplest parameter for evaluating the physiological conditions of animals under thermal stress. Genome-wide association studies (GWAS) have identified candidate genes related to economic traits in domestic animals. The present study conducted a GWAS on body temperature changes in a broiler-type strain Taiwan country chickens (TCCs) under acute heat stress. A total of two hundred 30-week-old roosters of a broiler-type strain TCCs were used. The roosters were subjected to acute heat stress at 38 °C for 4 h, and their body temperature was recorded before and during heat stress. The change in body temperature (ΔT) of each rooster was calculated according to the difference between the initial temperature and the highest body temperature during heat stress. The roosters were categorized according to survival and ΔT at the end into dead, susceptible, resistant, and intermediate groups. Collected red blood cells were genotyped using a 600 K chicken single-nucleotide polymorphism (SNP) array. A GWAS for ΔT was conducted using the Cochran-Armitage trend test. Significant SNPs were annotated as candidate genes according to the nearest genes. Results indicated that the ΔT of the heat-resistant group was significantly lower than that of the heat-susceptible group. A total of 17 SNPs belonging to 8 candidate genes, 352 SNPs for 78 candidate genes, and 174 significant SNPs for 63 candidate genes were identified in the association analyses in the dead vs. survival, resistant vs. susceptible, and intermediate vs. susceptible groups, respectively. The annotated candidate genes are associated with apoptosis, cellular response to external stimuli, and signal transduction pathways. In conclusion, the significant SNPs located in and proximal to genes in the GWAS analysis were related to apoptosis or responses to external stimuli which serve as potential candidates underlying physiological adaptation to heat stress or thermotolerance in chickens.